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Background and Study Aims:  Language is characteristically human, and preserving it is critical when resecting tumors in language-eloquent brain areas. Navigated repetitive transcranial magnetic stimulation (nrTMS) has been used in recent years as a noninvasive technique to identify preoperatively the language-eloquent cortical areas in tumor patients. An important objective is to increase the sensitivity and specificity of nrTMS in detecting language-related areas and increase the positive correlation of its results to that of intraoperative direct cortical stimulation (DCS). Although the technical aspects of the procedure have received enormous interest, factors related to the targeted cortical area such as previous cortical history or activity have been neglected. Therefore, the present study explores the impact of previous cortical history or activity on the effectiveness of a subsequent nrTMS mapping paradigm., Materials and Methods:  Twelve right-handed patients with a left hemispheric glioma underwent presurgical nrTMS language mapping and intraoperative language mapping with DCS. nrTMS was performed using a continuous theta burst stimulation paradigm to inhibit possible language relevant areas in the vicinity of the tumor, determined anatomically or based on functional magnetic resonance imaging hotspots. The nrTMS was applied in two separate sessions. One of the sessions randomly included a priming paradigm to precondition the targeted cortical areas., Results:  Priming stimulation decreased the error detection of the subsequent nrTMS mapping paradigm. This effect was more robust on major types of errors such as speech arrest and hesitation., Conclusion:  Prior cortical activity as induced by the priming stimulation has a profound impact on the responsiveness to the nrTMS mapping paradigm. Our findings further showed that metaplasticity, a type of homeostatic plastic process, could be elicited even in cortical areas affected by a growing tumor., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Continuous resting-state (RS) functional magnetic resonance imaging (fMRI) has become particularly useful to identify changes in functional connectivity (FC) in CNS disorders. Fair et al. proposed a method of volume extraction to emulate RS fMRI from block-design experiments. Whether the validity of this approach holds true in multiple sclerosis (MS) patients has not been tested formally so far. Twelve MS patients and 18 controls underwent conventional RS fMRI and a cognitive block-design fMRI. The total amount of volumes as well as the truncated set of volumes of both functional datasets was separately analyzed using a seed-based approach. Overall, seed-based analyses of FC from the anterior cingulated cortex allowed identification of the same key-network constituents using different analytical approaches, whereas higher-level within-group analyses of emulated RS versus continuous RS also revealed significant distinct differences in FC networks. Using the emulated RS approach, a general identification of connectivity networks similar to those obtained using conventional RS data also appears feasible in diseased brains. Higher-level contrasts, however, yielded different results attesting to a significant impact of employed methodology.

Background: Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology., Methods: 13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability., Results: Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance., Conclusions: Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.

Multiple sclerosis (MS) is a chronic inflammatory central nervous system disorder with a neurodegenerative component. While in the past, MS has been predominantly viewed as a white matter (WM) disease, gray matter (GM) pathology receives increasing attention in MS research. In this study, we tested hypothesis-free for a possible spatial relationship between cortical volume changes and disturbed integrity of projecting WM tracts. We used voxel-based morphometry (VBM), lesion probability maps (LPM), and probabilistic tractography to compare brain magnetic resonance imaging (MRI) scans obtained at 3 Tesla of 15 low disabled MS patients with 15 matched healthy controls (HCs). Areas of decreased cortical volume in the patients identified by VBM were used as seeds for tractography. Volume in two cortical areas in the left inferior frontal gyrus (IFG) and the left lateral occipital cortex (LOC) was reduced in patients compared to HCs. Starting from the IFG-region, tractography suggested impaired connections between left and right portions of the frontal lobe in the patients. Using the LOC as a seed, in patients, the left inferior longitudinal and fronto-occipital pathways appeared disintegrated compared to HCs. Swapping the seeds to homologous contralateral areas showed similar results for frontal, but different results for occipital brain areas. This at least partly could be explained by differential interference with WM lesions. These findings suggest a regional dependence between cortical GM and WM tract alterations in MS patients. While confirmation in larger and more heterogenic samples is needed, this study indicates that combining several MRI methods (VBM, LPM, and Probabilistic Tractography) may provide important insights into interacting processes related to the fiber tract and GM changes in MS.

Background: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this 'clinico-radiologic paradox'., Objectives: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing-remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions., Results: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location., Conclusions: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.